Dr Karen Forbes BSc, PhD

Normal development and function of the placenta is absolutely critical in achieving a successful pregnancy, for normal fetal growth depends directly on the transfer of nutrients from mother to baby via this organ. Although the insulin-like growth factors (IGFs) are known to be important for human placental growth and development, an understanding of their mode of action in placental biology remains to be established. The importance of acquiring insight into IGF signalling and placental function is dictated by the evidence that fetal growth disorders are rooted in defective placental development. Currently, there are no treatments for cases of altered fetal growth, and in order to make significant progress in this area a better understanding of the mechanisms regulating placental growth is needed.

Using a placental tissue explant model I have demonstrated that IGFs present in the maternal circulation, influence placental cell proliferation, apoptosis and differentiation through activation of multiple intracellular signaling pathways within the placenta. I have also developed methodologies to introduce short interfering RNA (siRNA) to human placental tissue; using these methods I have eliminated a number of proteins from the placenta and established that the ability of IGFs to regulate placental development is directly dependant on the presence of specific signalling molecules within the placenta. Manipulating the expression of IGF signalling molecules within the placenta may therefore provide therapeutic benefits for problem pregnancies.

Endogenously, gene expression can be regulated by microRNAs; the human placenta contains high levels of these molecules but their functions remain to be established. My research is now focused on:

• Establishing the key components of signalling cascades that are important for regulating normal placental development and function
• Understanding how placental signalling pathways are altered in pregnancies complicated by diabetes
• Investigating the role of microRNAs within the human placenta
• Identifying novel microRNAs within growth factor signalling cascades

For more information visit our lab webpage: http://www.medicine.manchester.ac.uk/aplinwestwood/research/placentalbiology/

PhD Physiology & Pharmacology, University of Strathclyde (2004)

BSc (Hons) Immunology & Pharmacology, University of Strathclyde (2001)

Affiliated staff and students

Christopher Fitzpatrick

PhD student. "Altering microRNAs to regulate placental development in pregnancies complicated by maternal diabetes." Co-supervised with Dr Melissa Westwood and Professor John Aplin.

Bernadette Baker

PhD student. "Folate deficiency in teenage pregnancy: Involvement in placental dysfunction." Co-supervised with Dr Rebecca Jones, Dr Susan Greenwood and Dr Alexander Heazell.

Joshua Jones

MRes student. " Profiling serum microRNAs to predict adverse outcomes in pregancies complicated by maternal diabetes." Co-supervised with Dr Melissa Westwood.

Collaborators

Dr Melissa Westwood

Senior Lecturer in Endocrinology, University of Manchester

Professor John Aplin

Professor of Reproductive Biomedicine, University of Manchester

Dr Rebecca Jones

Lecturer in Maternal and Fetal Health, University of Manchester